Potential Cure for Rheumatoid Arthritis Succeeds in Mouse Model

Researchers working with a mouse model of rheumatoid arthritis have identified a molecule with the potential to act as a chemotherapeutic agent for treatment of this devastating autoimmune disorder.

Investigators at Northwestern University (Chicago, IL, USA) worked with a line of mice that had been genetically engineered to lack the gene for a protein called Bim, an agent that mimics the action of Bcl-2 homology 3 (BH3) domain-only proteins. Such proteins have shown promise in preclinical studies of cancer and autoimmune disease treatment.

The expression of Bim was found to be reduced in synovial tissue from human rheumatoid arthritis patients as compared with controls, particularly in macrophages. Macrophages from mice lacking the Bim gene displayed elevated expression of inflammatory markers following stimulation with LPS (lipopolysaccharide) or thioglycollate.

In the current study, the investigators induced rheumatoid arthritis in mice lacking Bim expression. They reported in the February 2010 issue of the journal Arthritis & Rheumatism that treatment of these animals with exogenous Bim ameliorated rheumatoid arthritis symptoms. Furthermore, treatment with Bim prior to induction of arthritis prevented development of symptoms of the disease.

"This new therapy stopped the disease cold in 75% of the mice," said senior author Dr. Harris Perlman, associate professor of medicine at Northwestern University. "The best part was we did not see any toxicity. This has a lot of potential for creating an entirely new treatment for rheumatoid arthritis. The next step is to develop nanotechnology for a more precise method of delivering the drug."

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